- Brexanolone in Postpartum Depression:
- Sage is currently developing brexanolone in a Phase 3 clinical program as an acute interventional treatment for postpartum depression (PPD), consisting of separate multi-center, double-blind, placebo-controlled, randomized trials in severe PPD patients ( 202B) and in moderate PPD patients ( 202C), collectively known as the Hummingbird Study.
- Sage recently completed enrollment in its Phase 3 Hummingbird clinical program, and currently expects top-line results from the Phase 3 clinical trials of brexanolone in PPD to be the company's next data readout.
- SAGE-217 in Major Depressive Disorder:
- Sage is currently conducting a multi-center, double-blind, placebo-controlled, randomized Phase 2 clinical trial of SAGE-217 in major depressive disorder (MDD).
- Sage recently completed enrollment in the study, and expects to report top-line results in 4Q 2017.
- SAGE-217 in Postpartum Depression:
- Sage is currently conducting a multi-center, double-blind, placebo-controlled, randomized Phase 2 clinical trial of SAGE-217 in severe PPD.
- Completion of enrollment for the Phase 2 trial is expected in 4Q 2017 with top-line results expected in 1Q 2018.
- SAGE-217 in Parkinson's Disease:
- Sage today announced top-line results from an open-label Phase 2 clinical trial of SAGE-217 in patients with tremor-predominant Parkinson's disease.
- Part B of the exploratory study evaluated SAGE-217 as an adjunctive treatment for seven days in 14 tremor-predominant Parkinson's disease patients who were on stable doses of anti-Parkinsonian agents.
- SAGE-217 improved tremor symptoms, as assessed by the MDS-UPDRS - Part II/III tremor score, by a mean change of 7.7 points (40.0%) by Day 8 from a mean baseline score of 19.1 points, which was the primary efficacy endpoint in the Part B study.
- Additional secondary efficacy endpoints were consistent with the primary efficacy endpoint. SAGE-217 improved overall Parkinson's disease motor symptoms, as assessed by the MDS-UPDRS Part III motor score, by a mean change of 18.6 points (36.3%) by Day 8 from a mean baseline score of 52.4 points.
- SAGE-217 also improved symptoms of sleep dysfunction in five patients with clear sleep dysfunction at baseline, as assessed by the Parkinson's Disease Sleep Scale (PDSS-2) score, by a mean change of 12.2 points (41.2%) by Day 8 from a mean baseline score of 29.8 points.
- Administration of SAGE-217 in the evening was generally well-tolerated with no serious adverse events or discontinuations reported. The most common adverse events were dizziness, sedation, and somnolence, each occurring in two patients.
- Sage believes the results from this open-label Phase 2 trial support further clinical development, and that the data from this study will provide guidance on methodology, dosing, and design for a future placebo-controlled Phase 2 clinical trial in Parkinson's disease.
- SAGE-217 in Essential Tremor:
- Sage is currently conducting Part C of an exploratory Phase 2 clinical trial of SAGE-217 in essential tremor.
- Part A was an open-label trial with morning dosing of SAGE-217 for 7 days. Part A enrolled 16 patients diagnosed with essential tremor, defined as visible and persistent bilateral postural tremor and kinetic tremor, involving hands and forearms, with a duration greater than 5 years prior to screening. Part C is an open-label clinical trial that was initiated to study higher doses and extended evening dosing of SAGE-217. As a result of the change in design, enrollment in Parts A and B of the trial was discontinued prior to completion. The Part A data are summarized below.
- In Part A, SAGE-217 improved tremor symptoms, as assessed by the TETRAS upper limb combined kinetic score, by at least 30% on Day 7 in 8/12 patients (67%) who received SAGE-217 oral capsule in the study for 7 days, which was the pre-established success criteria for moving to the next part of the study.
- Administration of SAGE-217 in the morning was generally well-tolerated. The most common adverse events were somnolence, dizziness, and sedation. There were no serious adverse events reported in the 14 patients receiving SAGE-217 oral capsule. There was one serious adverse event (confusion) reported in one of the two patients who received oral solution.
- Top-line results from Part C of the SAGE-217 essential tremor study are expected in 4Q 2017.
- Sage is currently evaluating a series of novel GABA A receptor modulators in pre-clinical development, including SAGE-324, a novel, orally-active next-generation positive allosteric modulator of synaptic and extrasynaptic GABA A receptors.
- SAGE-324 is currently in IND-enabling studies, and is intended to be developed with a focus on orphan epilepsies and indications involving GABA hypofunction.
- Sage is also developing novel compounds that target the NMDA receptor. The first product candidate selected for development from this program is SAGE-718, a novel, oral, first-in-class oxysterol-based positive allosteric modulator of the NMDA receptor. Positive modulation of NMDA receptors may have potential in the treatment of a range of neurological disorders associated with a variety of cognitive, neurological and behavioral symptoms.
- Sage today announced that it recently completed a Phase 1 single-ascending dose study of SAGE-718 in healthy volunteers. The primary objectives of the study were to assess the safety, tolerability, and pharmacokinetics of SAGE-718.
- SAGE-718 was well-tolerated with no serious adverse events reported in the single ascending dose study.
- SAGE-718 was administered as an oral solution in four double-blind placebo-controlled cohorts (randomized 6:2) enrolling a total of 32 healthy volunteers. The pharmacokinetics of SAGE-718 were highly predictable with low variability.
- Based on these results, Sage plans to initiate a Phase 1 multiple ascending dose trial along with further dose finding studies. Sage is also investigating the effects of SAGE-718 on pharmacodynamic biomarkers.
- Top-Line Data Readouts:
- Phase 3 Hummingbird Study (202B) of brexanolone in severe PPD (4Q 2017)
- Phase 3 Hummingbird Study (202C) of brexanolone in moderate PPD (4Q 2017)
- Phase 2 trial of SAGE-217 in MDD (4Q 2017)
- Part C of Phase 2 trial of SAGE-217 in essential tremor (4Q 2017)
- Phase 2 trial of SAGE-217 in PPD (1Q 2018)
- Phase 1 multiple ascending dose trial of SAGE-718 (2H 2018)
- Cash Position: Cash, cash equivalents, and marketable securities as of September 30, 2017 were $243.5 million, compared with $397.5 million at December 31, 2016.
- R&D Expenses: Research and development expenses were $58.3 million, including $5.4 million of non-cash stock-based compensation expense, in the third quarter of 2017, compared to $29.1 million, including $2.5 million of non-cash stock-based compensation expense, for the same period of 2016. The increase in R&D expense was primarily due to the Phase 3 clinical development of brexanolone and CMC work in preparation for a potential filing for regulatory approval, the ongoing Phase 2 development of SAGE-217, ongoing early-stage R&D programs and discovery efforts focused on identifying new development candidates and additional indications of interest, and investments in R&D headcount to support the growth in Sage's pipeline and operations.
- G&A Expenses: General and administrative expenses were $16.1 million, including $4.3 million of non-cash stock-based compensation expense, in the third quarter of 2017, compared to $9.0 million, including $2.2 million of non-cash stock-based compensation expense, for the same period of 2016. The increase in G&A expenses was primarily due to the increase in personnel-related expenses, professional fees to support expanding operations, costs related to continued preparations for a potential commercial launch, and facilities-related costs to support expanding operations.
- Net Loss: Net loss was $73.7 million for the third quarter of 2017, compared to a net loss of $37.8 million for the same period of 2016.
|Sage Therapeutics, Inc. and Subsidiaries|
|Condensed Consolidated Balance Sheets|
|September 30, 2017||December 31, 2016|
|Cash and cash equivalents||$||134,916||$||168,517|
|Prepaid expenses and other current assets||4,892||5,100|
|Total current assets||248,343||402,579|
|Property and equipment and other long-term assets||2,742||1,952|
|Liabilities and Stockholders' Equity|
|Total current liabilities||49,837||35,169|
|Total stockholders' equity||200,052||368,517|
|Total liabilities and stockholders' equity||$||251,085||$||404,531|
|Sage Therapeutics, Inc. and Subsidiaries|
|Condensed Consolidated Statements of Operations|
|(in thousands, except share and per share data)|
|Three Months Ended September 30,||Nine Months Ended September 30,|
|Research and development||$||58,286||$||29,075||$||159,386||$||78,752|
|General and administrative||16,087||8,989||43,320||25,033|
|Total operating expenses||74,373||38,064||202,706||103,785|
|Loss from operations||(74,373||)||(38,064||)||(202,706||)||(103,785||)|
|Interest income, net||677||275||2,056||717|
|Other expense, net||(23||)||(7||)||(48||)||(18||)|
|Net loss per share - basic and diluted||$||(1.97||)||$||(1.15||)||$||(5.37||)||$||(3.20||)|
|Weighted average shares outstanding - basic and diluted||37,470,912||32,975,897||37,367,802||32,218,204|